Expression of prostate‐specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non‐polyglutamated folate, folic acid

  title={Expression of prostate‐specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non‐polyglutamated folate, folic acid},
  author={Veronica Yao and Clifford E Berkman and Joseph K. Choi and Denise S. O’Keefe and Dean Bacich},
  journal={The Prostate},
Prostate specific membrane antigen (PSMA) is a unique folate hydrolase that is significantly upregulated in prostate cancer. In a mouse model, PSMA is able to facilitate prostate carcinogenesis, however, little is known about the mechanism by which this occurs. As PSMA is able to hydrolyze polyglutamated folates, and cancer cells proliferate directly in response to available folate, we examined if expression of human PSMA in PC‐3 cells confers a proliferative advantage in a microenvironment… 

PSMA, a marker for prostate cancer: Molecular signalling and transport mechanisms in humans and their transferability to dogs

The results strongly propose an essential role for different types of membrane microdomains in homodimerization, internalization and signalling pathways involving PSMA.


Four major types of PSMA-specific ligands are discussed, including antibody, aptamer, peptide, and small molecule inhibitor, which have emerging applications in prostate cancer diagnosis, targeted drug delivery, and therapy.

Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

The goal of this study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer.

Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer

PSMA could be a new diagnostic and therapeutic alternative, particularly for triple-negative breast cancer, and appears to be a potential predictive and prognostic marker.

Antibody-drug conjugates targeting prostate-specific membrane antigen.

The preclinical and clinical findings have largely substantiated the promise of PSMA as an ADC target and potential future directions for ADCs that target PSMA are summarized.

The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease

The biological roles that PSMA/GCPII plays, both in normal and diseased tissues, and the current therapies exploiting its activity that are at the preclinical stage are discussed, as well as hurdles that need to be overcome to make them effective and viable.

The interplay between MDM2 and PSMA in metastatic breast cancer cells

Results indicate that MDM2, AKT and PSMA may represent a new pathway which could be targeted for therapy for breast tumours and perhaps other types of cancer.

Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer




Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro

This work studied if PSMA folate hydrolase activity provides cells a growth advantage in a low folate (LF) micro‐environment by hydrolyzing extracellular poly‐γ‐glutamated folate to a form that cells can import.

Prostate‐specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells

The prostate enzyme has activity in both the membrane and cytosolic fractions termed PSMA and PSMA′, respectively.

Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis.

The results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels, a novel mechanism that may contribute to the known role of folate in cancer prevention.

Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness.

In vitro invasion assays are used to explore the possible role of PSMA in the metastasis of prostate cancer cells and it seems that the enzymatic activity is associated with the effect of PSma on invasiveness.

Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells.

  • J. PintoB. Suffoletto W. Heston
  • Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1996
It is demonstrated clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3 and pteroylpentaglutamate as substrates and that cancer cells that express this enzyme are resistant to methotrexate therapy.

Use of Methotrexate-Based Peptide Substrates to Characterize the Substrate Specificity of Prostate-Specific Membrane Antigen (PSMA)

These studies have identified PSMA selective, plasma stable peptide substrates that can be incorporated into prodrugs targeted for activation by PSMA within prostate cancer sites.

Characterization of the enzymatic activity of PSM: Comparison with brain NAALADase

The NAAG hydrolyzing activity of NAALADase and the prostate enzyme PSM is compared to find out whether this enzyme cleaves terminal carboxy glutamates from both the neuronal peptide N‐acetylaspartyl glutamate (NAAG) and folate polyglutamate.

Prostate-Specific Membrane Antigen Regulates Angiogenesis by Modulating Integrin Signal Transduction

A novel role is identified for PSMA as a true molecular interface, integrating both extracellular and intracellular signals during angiogenesis, and it is shown that PSMA participates in an autoregulatory loop, wherein active PSMA facilitates integrin signaling and PAK activation, leading to both productive invasion and downregulation of integrin β1 signaling.

A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen.

It is suggested that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization, and it is shown that dominant negative micro2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalized of PSma mediated by the M XXXL motif.